Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients

Between 1978 and 1988, three patients at our institution had an initial diagnosis of idiopathic pulmonary fibrosis but later were correctly diagnosed as having pulmonary-renal syndrome and microscopic polyarteritis. These cases involved elderly patients with progressive dyspnea and nonproductive cough, bilateral dry crackling rales, bilateral interstitial infiltrates evident on a chest roentgenogram, and restrictive findings on pulmonary function testing. In two patients, lung biopsy specimens were obtained, and an initial diagnosis of nonspecific pulmonary fibrosis was made. All three patients eventually had microhematuria and renal insufficiency. A revised diagnosis of small-vessel pulmonary-renal vasculitis was based on the demonstration of segmental necrotizing glomerulonephritis in renal biopsy specimens in two patients, thrombotic microangiopathy consistent with healed vasculitis on postmortem examination of the kidney in one patient, and subsequent detection of small-vessel vasculitis on review of the two lung biopsy specimens. Anti-neutrophil cytoplasmic antibodies with perinuclear staining on indirect immunofluorescence microscopy were positive in the two patients in whom determinations were performed. The clinical manifestations of vasculitis were notably scarce--no involvement of the skin, nervous system, or gastrointestinal tract; no episodes of fever; and minimal or absent musculoskeletal symptoms. These cases illustrate the importance of a high index of suspicion for the diagnosis of systemic vasculitis in elderly patients and the need to consider a vasculitis in the differential diagnosis of idiopathic pulmonary fibrosis, especially if an active urinary sediment is present.     

Pulmonary vasculitis in the intensive care unit

Pulmonary vasculitis can occur in apparent isolation, as part of a primary systemic vasculitis, or with an underlying systemic inflammatory autoimmune disorder. The presentation of pulmonary vasculitis in the intensive care unit (ICU) can be fulminant and will often overlap with more common disorders that affect the critically ill. Although diffuse alveolar hemorrhage (DAH) is the clinical feature that often initiates the concern for an underlying vasculitis, hemoptysis may not be apparent or its presentation can be mistaken for an alternative disease process. As a result, the diagnosis of pulmonary vasculitis in the ICU may be delayed or be completely unrecognized. A high level of suspicion is essential to obtain a timely diagnosis and for effective therapies to be implemented. There have been significant advances this past decade in diagnostic strategies as well as in the therapeutic options for patients with pulmonary vasculitis. We review here the clinical presentations, diagnostic strategies, and treatment options of the critically ill patients presenting with pulmonary vasculitis. The reader is referred to other resources for a more comprehensive review of specific vasculitic entities.     

Cutaneous vasculitis: approach to diagnosis and systemic associations

The starting point in the evaluation of vasculitis is the clinical examination. The character and location of the primary lesions determine the type of biopsy specimens and additional tests needed to classify vasculitis. The most common causes of cutaneous vasculitis are drug reactions, infectious diseases, reactions to inflammatory diseases such as rheumatoid arthritis or inflammatory bowel disease, or association with malignant disease, especially lymphoproliferative disorders. Direct immunofluorescent techniques and leukocyte monoclonal antibody studies are useful for the diagnosis of selected cases of vasculitis. The clinical and histopathologic data help delineate an approach for further investigation of potentially associated systemic disorders or underlying causes. Although some cases of cutaneous vasculitis are not associated with systemic disorders, this possibility should never be assumed but considered only as a diagnosis of exclusion after careful examination of each patient.     

Headache and Vasculitis

Although headaches are common in the general population and have many causes, headaches secondary to inflammatory processes in the blood vessels in the Central Nervous System (CNS) are not so common. The most common types of vasculitis that are associated with headaches include primary CNS vasculitis, systemic necrotizing arteritis, granulomatous vasculitis, and systemic collagen diseases. It is important to differentiate between “true” vasculitides and a condition known and reversible cerebral vasoconstriction syndrome (RCVS). While treatment for many of the vasculitides consists of anti-inflammatory medications, this approach may produce significant complications in RCVS. It is up to the clinician to judiciously use imaging and laboratory data to reach the proper diagnosis and therefore offer the correct treatment to these patients.     

Complications maternelles graves des maladies systémiques auto-immunes

Systemic autoimmune diseases (SAID) mainly gathered connective tissue diseases with or without antiphospholipide syndrome scleroderma and systemic vasculitis. Commonly observed in systemic lupus, pregnancy is rare in vasculitis but some cases have been reported in Takayasu disease and in ANCA vasculitis. When the diagnosis is previously known, pregnancy must be carefully planned and monitored. Because pregnancy can lead to life threatening complications, some contraindications must be respected like renal insufficiency, severe hypertension, pulmonary arterial hypertension, severe cardiomyopathy or valvulopathy. Whereas pregnancy increases the risk of lupus flare, it seems not to influence the vasculitis activity. The mainly cause of intensive care unit admission in pregnant patients with SAID is infections due to the use of corticosteroids and/or immunosuppressive drugs. If flare of the disease is the cause of admission, women must usually be treated with high corticosteroid doses and if needed azathioprine because of its safety during pregnancy. Intravenous immunoglobulins and/or plasmapheresis are an interesting alternative in these situations with pathogenic autoantibodies. Maternal and foetal outcome is optimized by a multidisciplinary approach including intensivists, internists and obstetricians.     

Evaluation and treatment of vasculitis in the critically ill patient

The systemic vasculitides, if left untreated, often lead to major organ damage and death. When a patient presents with features that may be consistent with vasculitis, especially with pulmonary and renal findings, it is important to make a specific diagnosis as quickly as possible so that specific therapy can be started. Diagnosis is dependent on familiarity with the myriad of typical and unusual clinical features of the various vasculitides together with performance of supportive tests including serologies, angiograms, and biopsies. When evaluating a potential case of vasculitis, clinicians must comprehensively search for other more common, non-vasculitic diseases. The diagnosis may be even more difficult in patients with established diagnoses of vasculitis on immunosuppressive treatment who develop new clinical findings. Rapid initiation of immunosuppressive therapy for critically ill patients with vasculitis is crucial and may be life-saving.     

IgG4相关血管疾病的研究进展

IgG4相关疾病是一种自身免疫性疾病,常累及全身多部位的组织及器官。IgG4相关的血管炎常侵犯多部位的血管,以主动脉及其一级分支为主,并容易合并动脉瘤,动脉瘤的破裂会有致命风险。在诊断上,需鉴别IgG4相关的血管炎与其他常见血管炎;在治疗上,激素虽然是治疗IgG4相关的血管炎的基石,但也会加快某些患者血管瘤的破裂,因此,临床上需结合介入及外科手术等方法综合治疗。     

An approach to diagnosis and initial management of systemic vasculitis.

Systemic vasculitis occurs in a heterogeneous group of primary disorders or can be a manifestation of infection, an adverse drug reaction, malignancy or a connective tissue disease. A vasculitic process should be suspected in patients with unexplained ischemia or multiple organ involvement, especially when such features as polymyalgia rheumatica, inflammatory arthritis, palpable purpura, glomerulonephritis or multiple mononeuropathy are also present. The clinical features of systemic vasculitis depend on the organs involved and, in turn, organ involvement is largely influenced by the size of the affected blood vessels. The diagnostic work-up should be tailored to the clinical situation and geared toward a tissue or angiographic diagnosis, bearing in mind that the findings from these studies are not always pathognomonic. Emphasis should also be placed on exclusion of a secondary process. The diagnosis of the specific type of vasculitis may be made on the basis of the clinical features and the histopathologic or angiographic findings. Initial therapy for most types of systemic vasculitis consists of high-dose corticosteroids, with the addition of immunosuppressive therapy in certain patients.     

My Treatment Approach to Giant Cell Arteritis

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in adults 50 years or older. Expanded use of advanced arterial imaging has assisted both in the diagnosis of GCA and recognition of disease subsets. Although glucocorticoids have been the mainstay of treatment for almost 7 decades, new therapeutic options have emerged. This review aims to provide the clinician with a pragmatic approach to evaluating and managing patients with GCA while also addressing recent diagnostic and therapeutic developments.     

The aspects of the problem of systemic vasculitis open to discussion

Some controversial problems in the diagnosis of systemic vasculitis are discussed. The importance of the morphological studies is assessed. The data are provided on the interrelations between skin and systemic vasculitis, on the existence of the local forms of vasculitis, the presence of the crisscross, mixed and combined forms of vasculitis, and on the possibility of the primary chronic disease course. The data obtained are based on the results of the prolonged observation over 325 patients suffering from systemic vasculitis.     

ANCA-associated small-vessel vasculitis

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common primary systemic small-vessel vasculitis to occur in adults. Although the etiology is not always known, the incidence of vasculitis is increasing, and the diagnosis and management of patients may be challenging because of its relative infrequency, changing nomenclature, and variability of clinical expression. Advances in clinical management have been achieved during the past few years, and many ongoing studies are pending. Vasculitis may affect the large, medium, or small blood vessels. Small-vessel vasculitis may be further classified as ANCA-associated or non-ANCA-associated vasculitis. ANCA-associated small-vessel vasculitis includes microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome, and drug-induced vasculitis. Better definition criteria and advancement in the technologies make these diagnoses increasingly common. Features that may aid in defining the specific type of vasculitic disorder include the type of organ involvement, presence and type of ANCA (myeloperoxidase-ANCA or proteinase 3-ANCA), presence of serum cryoglobulins, and the presence of evidence for granulomatous inflammation. Family physicians should be familiar with this group of vasculitic disorders to reach a prompt diagnosis and initiate treatment to prevent end-organ damage. Treatment usually includes corticosteroid and immunosuppressive therapy.     

Coronary artery vasculitis: assessment with cardiac multi-detector computed tomography

Coronary artery vasculitis is rare and comprises an array of inflammatory diseases. It often results in severe and life-threatening complications, including coronary artery aneurysm, coronary artery stenosis, intraluminal thrombosis, and microcirculation abnormalities. These may occur at a young age and are often silent in the early phases. Invasive coronary angiography is the gold standard for diagnosing coronary artery disease (CAD); however, multi-detector computed tomography (MDCT) is now widely regarded as a powerful non-invasive tool for the detection of CAD. It is important for clinicians to recognize the various CT findings associated with coronary artery vasculitis in order to promote accurate diagnosis and proper patient management. The purpose of this article is to present an overview of the conditions associated with coronary artery vasculitis, with an emphasis on etiology and cardiac MDCT diagnosis of CAD. Cardiac MDCT is clinically useful and can provide information for the accurate diagnosis and treatment of coronary vasculitis.     

Cerebral vasculitis--recognition, diagnosis and management

Cerebral vasculitis is a serious but uncommon condition which presents considerable difficulties in recognition, diagnosis and treatment. We studied eight consecutive patients in whom this diagnosis was made. Despite the great diversity of symptoms and signs, we noted three clinical patterns: (i) acute or sub-acute encephalopathy, (ii) a picture with some similarities to multiple sclerosis ('MS-plus'), and (iii) features of a rapidly progressive space-occupying lesion. The identification of these patterns may help recognition of cerebral vasculitis. The diagnostic value of four investigative procedures not previously studied in cerebral vasculitis was assessed: ophthalmological examination using low-dose fluorescein angiography with slit-lamp video microscopy of the anterior segment (abnormal in 4/5 patients); spinal fluid oligoclonal band analysis (abnormal in 3/6 patients); anti-neutrophil cytoplasmic antibody assay (abnormal in 3/8 patients); and indium-labelled white-cell cerebral imaging (positive in only one patient). Treatment was with steroid alone (n = 2) or steroid with cyclophosphamide (n = 6). Seven patients responded clinically.      

New strategies for plasma exchange in systemic vasculitis

The use of plasma exchange in the treatment of systemic vasculitis has been controversial and poorly defined. Since the discovery of anti-neutrophil cytoplasm antibodies (ANCA) and the demonstration of their specificity for systemic vasculitis, there has been a reassessment of the use of plasma exchange along the same lines as its use in anti-glomerular basement membrane disease. ANCA has also contributed to the diagnosis and classification of rapidly progressive glomerulonephritis, in which there is now firmer evidence to support the use of plasma exchange. Current work into the immunoregulation of ANCA by idiotype/anti-idiotype interactions is leading to new approaches to therapy and plasma exchange alone appears capable of inducing prolonged remission in some patients with vasculitis, possibly through an effect on these interactions.     

Incidence of Leukocytoclastic Vasculitis, 1996 to 2010: A Population-Based Study in Olmsted County,Minnesota

ObjectiveTo determine the population-based incidence of leukocytoclastic vasculitis (LCV).Patients and MethodsThis is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy–proven diagnosis of LCV from January 1, 1996, through December 31, 2010.ResultsA total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy–proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody–associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 [44%]). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03).ConclusionThe incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.     

老年ANCA相关性小血管炎肺损害11例临床分析

目的探讨老年抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎肺脏损害的临床特征,提高对其肺损害的认识。方法回顾性分析北京大学第一医院老年科60岁以上的ANCA相关性小血管炎肺损害患者的临床病理资料。结果11例ANCA相关性小血管炎肺脏损害患者平均年龄75.9(60～89)岁,均有慢性基础病。发病至确诊的中位间隔时间为4个月(2周～1年)。小血管炎临床症状多为咳嗽、咯痰(90.9%);喘憋气短或活动耐力下降(63.6%);咯血/痰中带血(36.4%)和发热(45.5%)。胸部影像学9例(91.9%)表现为肺间质病变,其中8例呈显著肺纤维化表现;2例(18.2%)呈两肺大片渗出的弥漫肺泡出血表现(其中1例在肺纤维化基础上发生);1例呈结节性病变(9.1%)。8例(72.7%)患者初诊时无肾损害。确诊主要依靠血清ANCA的检测和组织活检病理诊断。经免疫抑制治疗后,多数患者症状好转,初诊及随访期间5例(45.5%)因呼吸衰竭或严重感染死亡。结论原发性ANCA相关性小血管炎患者常有肺部受累并可以为首发表现。其症状和胸部影像表现多样,肺间质病变突出。正确及时的诊断治疗能改善预后。     

ANCA相关性血管炎肾损害合并交通性脑积水一例并文献复习

目的 探讨合并交通性脑积水的ANCA相关性血管炎（AAV）的发病机制、诊治方法,提高临床医师对AAV罕见类型的认识水平。方法 收集1例以交通性脑积水为首发症状的AAV病例的临床资料,以“ANCA相关性血管炎”“脑积水”为关键词（包括中英文）对PubMed和CNKI收录的论文进行检索,结合文献分析病例特点、实验室检查、影像学检查、肾脏活组织检查（活检）和诊治方法。结果 该例71岁男性患者,因头晕伴行走不稳半年余在门诊行CT检查提示交通性脑积水,拟行手术治疗。术前检查发现血清肌酐635 μmol/L,核周型-抗中性粒细胞胞质抗体（p-ANCA）（+）,MPO 293 U/L,尿红细胞位相示畸形红细胞240 000 /μL,经肾脏活组织检查（活检）证实存在AAV肾损害。随访30个月,经糖皮质激素（激素）联合环磷酰胺治疗后,患者血清肌酐降至335 μmol/L并脱离透析,头晕、行走不稳、智力减退症状逐渐好转,后多次复查颅脑MRI,交通性脑积水较前无明显变化。检索数据库后共收集5篇相关病例报道,患者年龄33~76岁,临床表现为脑积水和AAV,予激素联合免疫抑制剂、脑室-腹膜分流术等治疗,随访期间1例患者死亡,另外4例患者症状缓解。结论 以脑积水起病的AAV罕见且血管炎症状隐匿,易被误诊或漏诊,对不明原因伴肾衰竭的神经系统受累病变进行ANCA筛查十分必要,肾穿刺活检有助于明确诊断,及时正规治疗可缓解脑积水症状,有助改善患者预后。     

Cutaneous leukocytoclastic vasculitis: clinical experience in 44 patients

Chronic or recurrent cutaneous leukocytoclastic vasculitis is one of the more difficult therapeutic challenges to the practicing dermatologist. We have used a variety of therapeutic agents to treat 44 patients with leukocytoclastic vasculitis who had chronic or recurrent disease of more than three months' duration. Sixteen cases were classified as urticarial vasculitis based on the major clinical manifestations, while the remaining 28 cases represented various patterns. Effectiveness of treatment was graded according to resolution of lesions, return to normal of abnormal laboratory findings, or the ability to lower the dosage of a second therapeutic agent (usually a corticosteroid). Systemic corticosteroids, azathioprine, and colchicine appeared to be effective in most patients. Nonsteroidal anti-inflammatory agents, sulfones, antihistamines, and antimalarials were effective only in sporadic cases. We present an approach to the treatment of this type of disorder.     

肺血管炎361例临床分析

目的探讨肺血管炎的临床特点。方法回顾性分析361例肺血管炎患者的临床资料,观察疾病特点及在民族、性别等方面的差异。结果肺血管炎女性发病率（85.6%）高于男性（14.4%）（P〈0.05）,汉族、维吾尔族、哈萨克族和回族肺血管炎发病率（54.8%、28.3%、11.9%、4.99%）比较差异无统计学意义（P〉0.05）;咳嗽、发热为肺血管炎常见临床症状,其中121例有多脏器受累,可继发于系统性红斑狼疮、类风湿性关节炎、干燥综合征等疾病;肺部高分辨率CT可见网状改变、肺泡病变、囊状改变及结节改变;抗中性粒细胞胞质抗体阳性63例（17.5%）。结论肺血管炎发生率在民族间未发现存在差异,多见于女性,临床症状不典型,有多脏器受累的特点;动态检测抗中性粒细胞胞质抗体或行组织活检病理检查有助于疾病的诊断。     

Vasculitis Associated With Tumor Necrosis Factor-α Inhibitors

ObjectiveTo describe the clinical characteristics, histopathologic features, and outcomes of patients in whom vasculitis developed in association with use of tumor necrosis factor-α (TNF-α) inhibitors.Patients and MethodsThis is a retrospective review of patients evaluated at Mayo Clinic, Rochester, Minnesota, from January 1, 1998, through March 31, 2011, with a diagnosis of vasculitis induced by anti–TNF-α therapy.ResultsOf 8 patients with vasculitis associated with anti–TNF-α therapy (mean age, 48.5 years), 6 (75%) were female. Four (50%) had rheumatoid arthritis, 1 (13%) had Crohn disease, and 3 (38%) had ulcerative colitis. Five (63%) were treated with infliximab, 2 (25%) with etanercept, and 1 (13%) with adalimumab. The mean duration of treatment before development of vasculitis was 34.5 months. The skin was the predominant organ affected (5 patients [63%]), with the most common cutaneous lesion being palpable purpura (4 of 5 [80%]). Two organs involved in systemic vasculitis were the peripheral nervous system (4 patients [50%]) and kidney (1 patient [13%]). All cases of vasculitis were histopathologically confirmed. Seven of 8 patients improved with discontinuation of therapy (mean time to resolution, 6.9 months) and adjuvant treatment (all 8 received prednisone; another agent was also used in 7); rechallenge with anti–TNF-α therapy was not attempted in any patient. At last follow-up, no patients had experienced a recurrence of vasculitis after therapy discontinuation.ConclusionCutaneous small-vessel vasculitis was the most common finding, but systemic vasculitis, including peripheral nerve and renal vasculitis, was also frequently observed.